Transdermal drug delivery systems have, in recent years, become an increasingly important means of administering drugs. Such systems offer advantages clearly not achievable by other modes of administration such as avoiding introduction of the drug through the gastro-intestinal tract or punctures in the skin to name a few.
Presently, there are two types of transdermal drug delivery systems, i.e., “Passive” and “Active.” Passive systems deliver drug through the skin of the user unaided, an example of which would involve the application of a topical anesthetic to provide localized relief, as disclosed in U.S. Pat. No. 3,814,095 (Lubens). Active systems on the other hand deliver drug through the skin of the user, such as a patient, using iontophoresis, which according to Stedman's Medical Dictionary, is defined as “the introduction into the tissues, by means of an electric current, of the ions of a chosen medicament.”
Conventional iontophoretic devices, such as those described in U.S. Pat. No. 4,820,263 (Spevak et al.), U.S. Pat. No. 4,927,408 (Haak et al.) and U.S. Pat. No. 5,084,008 (Phipps), the disclosures of which are hereby incorporated by reference, for delivering a drug or medicine transdermally through iontophoresis, basically consist of two electrodes—an anode and a cathode. Usually, electric current is driven from an external supply into the skin at the anode, and back out at the cathode. Accordingly, there has been considerable interest in iontophoresis to perform delivery of drugs for a variety of purposes. Two such examples, involve the use of Novocaine,™ which is usually injected prior to dental work to relieve pain, and Lidocaine,™ which is usually applied as a topical, local anesthetic.
Such prior devices have prior hereto not been pre-loaded and self adhering, e.g., they have typically utilized an absorbent pad or porous solid sheet that can be filled with drug solution as the drug reservoir. These absorbent pads or porous sheets have three major disadvantages. First, they must be filled with the drug solution after removal from the package since these pads or porous sheets do not hold the drug solution as the solution is subject to removal and leakage under pressure or flexure. In addition, even after the inconvenient addition of the drug solution and after removal from the package, the absorbent pad or porous sheet reservoir remain subject to leakage and smearing of the drug solution due to pressure or flexure upon the skin. Furthermore, absorbent pads or porous solid sheets can not provide the electrical continuity to complete intimate contact since they lack adhesiveness and flexibility with the skin and its contours.
In addition, prior drug reservoirs have included pastes and unformed viscous semi-solid gels such as for example agar that have both solid and liquid characteristics as described, for example, in U.S. Pat. No. 4,383,529 (Webster), the disclosure of which is hereby incorporated by reference.
Powers et al., U.S. Pat. No. 4,886,277, although suggesting that Lidocaine could be incorporated into the reservoir, fails to solve the resulting problem associated with compatibility with adjacent materials such as conductive layers. Accordingly, such a device would fail to provide sufficient stability for extended shelf life, i.e., more than one year.
However, several disadvantages and limitations have been associated with the use of such devices, including handleability and loadability. For example, the semi-solid agar reservoir disclosed in Webster flows under shear or stress. Furthermore, this disclosed reservoir may melt upon exposure to modest elevated temperatures. The agar is unstable, spontaneously releasing aqueous solution.
Thus, there has been a need for an iontophoretic drug delivery device and a reservoir for use in the same, as well as a method for making the reservoir, which would eliminate the problems and limitations associated with the prior devices discussed above, most significant of the problems being associated with stability, handleability, loadability and electrocontinuity of the reservoir, including chemical and thermal stability of the reservoir and the electrode.